The MSKCC Brain tumor SPORE includes 6 research projects and 5 supportive cores. Research Project 1 (RP1) addresses the correlation between glial cell differentiation and the formation of low-grade gliomas and whether blockade of the pathways preventing differentiation will have therapeutic effect. RP2 addresses the correlation between signal transduction abnormalities and the formation of glioblastoma. We will determine whether blockade of these pathways will have a therapeutic effect on GBMs generated by Akt and Ras signaling in mice and in humans. RP3 uses genetically engineered mice and human tumor samples to understanding the molecular abnormalities leading to the vascular changes seen in GBMs, specifically integrin signaling, the function of the Id genes and Hifl alpha. In RP4 we will develop serum markers that detect the presence of gliomas and distinguish grade and tumor burden. In this project, we will identify candidate genes that are GBM specific on a microarray analysis and measuring the serum levels of the gene products by ELISA, and we will also use proteinomic analysis of patient's serum directly and identify proteins that are specifically found in subsets of glioma patients. RP5 involves the prediction and measurement of cognitive dysfunction as a result of radiation therapy for gliomas. We will follow the cognitive function of patients after radiation therapy and determine if their APOE allele correlates with the development of cognitive dysfunction and could therefore be used as a predictive marker for poor cognitive outcome following radiation therapy. We will also measure the diffusion weighted magnetic imaging and MR spectroscopy to determine if either of these modalities will be capable measuring biologic correlates of cognitive dysfunction. RP6 involves the development of imaging strategies for measuring signal transduction in vivo. In this project this technology will be developed in the mouse and the ability to measure the reporter in human gliomas will be determined. The Pathology Core will bank and distribute patient serum and tumor specimens from surgical resection. In order to expand the tumor bank available for SPORE, this core will be include specimens from both MSKCC and NYU and will be jointly run by Project Leaders from both Institutions. The imaging core will be involved in imaging the animals in the preclinical trials of RP1, RP2, and RP3 as well as imaging the patients in RP5. The clinical trials core will provide support for the clinical trials in RP1, RP2, and RP4. The statistical core will provide support for both the human and animal trials of all the projects and the administrative core will provide administrative support for the entire SPORE program.